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Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression

Circulating tumor cells (CTCs) are promising biomarkers for prognosis, therapeutic response prediction, and treatment monitoring in cancer patients. Despite its epithelial origin, renal cell carcinoma (RCC) shows low expression of epithelial markers hindering CTC-enrichment approaches exploiting epi...

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Autores principales: Cappelletti, Vera, Verzoni, Elena, Ratta, Raffaele, Vismara, Marta, Silvestri, Marco, Montone, Rosanna, Miodini, Patrizia, Reduzzi, Carolina, Claps, Melanie, Sepe, Pierangela, Daidone, Maria Grazia, Procopio, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073151/
https://www.ncbi.nlm.nih.gov/pubmed/32098246
http://dx.doi.org/10.3390/ijms21041475
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author Cappelletti, Vera
Verzoni, Elena
Ratta, Raffaele
Vismara, Marta
Silvestri, Marco
Montone, Rosanna
Miodini, Patrizia
Reduzzi, Carolina
Claps, Melanie
Sepe, Pierangela
Daidone, Maria Grazia
Procopio, Giuseppe
author_facet Cappelletti, Vera
Verzoni, Elena
Ratta, Raffaele
Vismara, Marta
Silvestri, Marco
Montone, Rosanna
Miodini, Patrizia
Reduzzi, Carolina
Claps, Melanie
Sepe, Pierangela
Daidone, Maria Grazia
Procopio, Giuseppe
author_sort Cappelletti, Vera
collection PubMed
description Circulating tumor cells (CTCs) are promising biomarkers for prognosis, therapeutic response prediction, and treatment monitoring in cancer patients. Despite its epithelial origin, renal cell carcinoma (RCC) shows low expression of epithelial markers hindering CTC-enrichment approaches exploiting epithelial cell surface proteins. In 21 blood samples serially collected from 10 patients with metastatic RCC entering the TARIBO trial, we overcame this limitation using the marker-independent Parsortix™ approach for CTC-enrichment coupled with positive and negative selection with the DEPArray™ with single cell recovery and analysis for copy number alterations (CNA) by next generation sequencing NGS. Two CTC subpopulations were identified: epithelial CTC (eCTC) and non-conventional CTC (ncCTC) lacking epithelial and leukocyte markers. With a threshold ≥1CTC/10 mL of blood, the positivity rates were 28% for eCTC, 62% for ncCTCs, and 71% considering both CTC types. In two patients with detectable eCTCs at baseline, progression free survival was less than 5 months. In an index case, hierarchical structure by translational oncology (TRONCO) identified three clones among 14 CTCs collected at progression and at baseline, each containing cells with a 9p21.3loss, a well-known metastasis driving subclonal alteration. CTCs detection in RCC can be increased by marker-independent approaches, and CTC molecular characterization can allow detection of subclonal events possibly related to tumor progression.
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spelling pubmed-70731512020-03-19 Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression Cappelletti, Vera Verzoni, Elena Ratta, Raffaele Vismara, Marta Silvestri, Marco Montone, Rosanna Miodini, Patrizia Reduzzi, Carolina Claps, Melanie Sepe, Pierangela Daidone, Maria Grazia Procopio, Giuseppe Int J Mol Sci Article Circulating tumor cells (CTCs) are promising biomarkers for prognosis, therapeutic response prediction, and treatment monitoring in cancer patients. Despite its epithelial origin, renal cell carcinoma (RCC) shows low expression of epithelial markers hindering CTC-enrichment approaches exploiting epithelial cell surface proteins. In 21 blood samples serially collected from 10 patients with metastatic RCC entering the TARIBO trial, we overcame this limitation using the marker-independent Parsortix™ approach for CTC-enrichment coupled with positive and negative selection with the DEPArray™ with single cell recovery and analysis for copy number alterations (CNA) by next generation sequencing NGS. Two CTC subpopulations were identified: epithelial CTC (eCTC) and non-conventional CTC (ncCTC) lacking epithelial and leukocyte markers. With a threshold ≥1CTC/10 mL of blood, the positivity rates were 28% for eCTC, 62% for ncCTCs, and 71% considering both CTC types. In two patients with detectable eCTCs at baseline, progression free survival was less than 5 months. In an index case, hierarchical structure by translational oncology (TRONCO) identified three clones among 14 CTCs collected at progression and at baseline, each containing cells with a 9p21.3loss, a well-known metastasis driving subclonal alteration. CTCs detection in RCC can be increased by marker-independent approaches, and CTC molecular characterization can allow detection of subclonal events possibly related to tumor progression. MDPI 2020-02-21 /pmc/articles/PMC7073151/ /pubmed/32098246 http://dx.doi.org/10.3390/ijms21041475 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cappelletti, Vera
Verzoni, Elena
Ratta, Raffaele
Vismara, Marta
Silvestri, Marco
Montone, Rosanna
Miodini, Patrizia
Reduzzi, Carolina
Claps, Melanie
Sepe, Pierangela
Daidone, Maria Grazia
Procopio, Giuseppe
Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression
title Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression
title_full Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression
title_fullStr Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression
title_full_unstemmed Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression
title_short Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression
title_sort analysis of single circulating tumor cells in renal cell carcinoma reveals phenotypic heterogeneity and genomic alterations related to progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073151/
https://www.ncbi.nlm.nih.gov/pubmed/32098246
http://dx.doi.org/10.3390/ijms21041475
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